Neuropeptide Y attenuates naloxone-precipitated morphine withdrawal via Y5-like receptors.
The effects of intracerebroventricular injection of neuropeptide Y (NPY) and various NPY-related peptides were studied on naloxone-precipitated withdrawal from morphine in rats. The withdrawal reaction was assessed using an overall motor score, including jumping, wet dog shakes and other motor-related signs as well as a nonmotor score. At doses of 3, 6 or 12 nmol, NPY strongly and dose-dependently reduced the motor score. A less prominent inhibitory effect was revealed on the nonmotor score. At 6 nmol, [Leu31,Pro34]-NPY, NPY 3-36, peptide YY and human pancreatic polypeptide all significantly attenuated the motor score, whereas NPY 13-36 was without effect. This pharmacological profile suggests that the antiwithdrawal effect of NPY is mediated via the recently cloned Y5 receptor. Our data are consistent with a potential role for NPY and Y5-like receptors in basic mechanisms and as a therapeutic target in opioid dependence and withdrawal.
Woldbye
D P
DP
Laboratory of Neuropharmacology, Department of Pharmacology, University of Copenhagen,, Rigshospitalet, Copenhagen, Denmark.
Klemp
K
K
Madsen
T M
TM
D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D009020:Morphine / Q000009:adverse effects*; D009043:Motor Activity / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D009478:Neuropeptide Y / Q000502:physiology*; D019894:Peptide YY / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017476:Receptors, Neuropeptide Y / Q000502:physiology*; D013329:Structure-Activity Relationship; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*
D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C100568:neuropeptide Y5 receptor; D019894:Peptide YY; D009270:Naloxone; D009020:Morphine